Syntheses Utilizing Cyclopentadiene

Halides and other salts as well as metal carbonyls sometimes react with cyclopentadiene to afford cyclopentadienyl complexes with concomitant evolution of hydrogen, hydrogen chloride, or other reduction products, such as CjHg. These reactions take place under relatively severe conditions at high temperatures and often under elevated pressures  

During reactions with metal carbonyls, cyclopentadiene complexes are probably first formed which subsequently undergo rearrangement to hydridocyclopentadienyl compounds followed by decomposition with hydrogen evolution  

It is possible that in some syntheses, the ligands may play the role of a base abstracting the proton. 

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An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

Recently, Mander and coworkers [122] reported the total synthesis of sordaricin (4-347), the aglycone of the potent antifungal diterpene sordarin which was first isolated in 1971 from the ascomycete Sordaria araneosa. Two approaches were explored the first method utilized a possible biogenetic Diels-Alder reaction the second was based on a domino retro-Diels-Alder/intramolecular Diels-Alder process. Thus, heating of 4-348 led, with extrusion of cyclopentadiene, to a 1,3-butadiene as intermediate which underwent an intramolecular Diels-Alder reaction to give the desired 4-349 as the main product, together with a small amount of 4-350 (Scheme 4.77). 

A special class of synthesis is the utilization of retro-Diels-Alder (RDA) reactions. A double RDA sequence was used to prepare the pyrimido[l,2-A]pyridazin-3-one 118. In this versatile method both reactants of the parent compound were constructed from cyclopentadiene. The parent compound 117 contains two norbornene units and decomposes on heating in toluene in a double RDA reaction leaving two double bonds in the target heterocycle. Similarily, the parent compound 119 decomposes in a single RDA reaction to yield the benzologue, pyridazino[6,l-3]-quinazolin-10-one 120 (Scheme 13) <2000SL67>. 

CH2CpCo(C0)2 3 and CpCo(C0)2 were prepared utilizing the procedures of Grubbs et al. for the syntheses of poly-styrene-bound cyclopentadiene (25) and Rausch and Genetti for the synthesis of CpCo(C0)2 (26 ). Thus, for 3, commercially available (P)CH2C1 (1% DVB, microporous, 1.48 mmol Cl/g. resin) was treated with excess NaCp to form CH2CpH 2. This was then exposed to Co2(C0)e to form desired compound 3 (0.3-0.5 mmol Co/g. resin,... 

Corey and Ishihara29 report the synthesis of a new bis(oxazoline). This catalyst effects Diels-Alder reaction via a tetracoordinated metal complex. Ligand (.S )-8I is synthesized from (iS )-phenylglycine, as depicted in Scheme 5-25. Treatment of 81 with Mgl2 L gives a dark solution of complex 82, which can be utilized as a Diels-Alder reaction catalyst. Thus, reaction of cyclopentadiene with 71 in the presence of 82 yields product 72a with an enantiomeric ratio of over 20 1 (Scheme 5-26). 

There are cases known in which the use of different precursors of 221 was not equally successful in the synthesis of a certain cydoadduct. Thus, when the bromo-fluorocyclopropane 239 and 1,3-cyclopentadiene were employed as source and trapping reagent for 221, respectively, the diene was deprotonated to a large extent [66, 139], whereas this process did not play a major part on utilization of the dibromocy-clopropane 254 (Scheme 6.55). Further, an experiment to prepare the furan adducts 231-233 (Scheme 6.53) from 239 failed [66], probably because of the metalation of furan by MeLi or the carbenoid resulting from 239. 

More recent developments have utilized metal vapor synthesis (method F) involving cocondensation at low temperature of the metal, cyclopentadiene (or other dienes), and PF3. The hydrido-cyclooctadienyl complex [Cr( 5-C8Hn)(PF3)3H] 125) (see Section IX) made in this fashion exhibits variable-temperature NMR spectra which establish the existence of an exchange between the hydrido atom and a methylenic hydrogen bound to an sp3 carbon adjacent to the diene unit. 

After Buchi confirmed this finding in the 19S0s, numerous other investigators immediately recognized the rapidity with which complex molecular architectures could be constructed by this reaction. Cookson irradiated the Diels-Alder adduct (3) of cyclopentadiene and benzoquinone to produce the caged diketone (4) (equation 2) while Eaton utilized a photochemical cycloaddition of diene (5) in a synthesis of the platonic solid cubane (6) (equation 3). ... 

Cyclopropanones act as three-carbon sources in [4 + 3] cycloadditions. However, these small-ring compounds are impractical for preparative scale experiments, because they are generally inaccessible and also must be handled with special precautions, in contrast to other oxyallyl species. One of the early descriptions of the synthesis of cyclopropanones appeared in 1932. NeverAeless, the development of the chemistry of cyclopropanones proceeded at quite a slow pace until the late 1960s when Turro reported their utilization in [4 -i- 3] cycloaddition reactions. 2,2-Dimethylcyclopropanone (14) adds to furan, cyclopentadiene, 6,6-dimethylfulvene and the relatively nucleophilic N-methylpyrrole to give the corresponding cycloproducts, but fails to react with anthracene and 1,3-butadiene. Parent cyclopropan-one cannot be used. 

A total synthesis of the herbindoles, strucmrally related cyclopent[g]indole natural products, utilized a t3qre la condensation reaction <05OL1215>. Treatment of quinone imine 94 with cyclopentadiene produced cycloadduct 95 which cycUzed to indole 96 in the presence of hydrochloric acid. The latter was elaborated into ( )-c -tiikentrin B 97. 

The utility of such cycloadditions has been demonstrated by the elaboration of the cycloadducts to complex natural products [60]. For example, the adduct derived from a cyclopentadiene having a 2-bromoallyl sidechain has been converted to an intermediate employed in a previous (racemic) synthesis of gibberel-lic acid. As illustrated in Scheme 12, an exceptionally efficient synthesis of cassi-ol is realized by the successful execution of a rather difficult endo-selective Diels-Alder reaction using a slightly modified oxazaborolidine (11). The high catalyst loading is balanced by the fact that all the carbons and the quaternary center of the natural product are introduced in a single step. 

The endo cycloadducts resulting from the cycloaddition of optically active 3-(2-pyridylsulfinyl)acrylates and simple dienes such as cyclopentadiene and furan have been utilized successfully in the asymmetric synthesis of several natural products [166-170]. For example, cycloadduct (197), synthesized as a single diastereoisomer from the reaction of (5)-3-(2-pyridylsulfinyl)acrylate with cyclopentadiene, was converted to the lactone (198) [166], a key intermediate in the synthesis of the carbocyclic nucleosides (-)-aristeromycin (199) and (-)-neplanocin A (200) (Scheme 5.65) [167]. 

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